Still-Gennari

The trisubstituted (Z)-olefin was introduced by Still-Gennari HWE olefination, as precedented by Schreiber [43, 44, 106], and following silyl protection provided 124. Conversion into the iodide 125 was followed by alkylation with the lithium enolate of aryl ester 126, to complete the C9-C16 subunit 121. The synthesis of the C17-C24 subunit 98 from 120 began with a four-step sequence involving protecting group manipulations and oxidation at C21 to provide aldehyde 127, converging with the earlier route to 98 [55-57],... 

As outlined in Scheme 28, the synthesis of the P-ketophosphonate 131 began with a one-pot anh -aldol/reduction step between ethyl ketone 101 and aldehyde 133, giving the 1,3-syn diol 134 (>30 ldr) [130, 132-136, 145, 146], The diol 134 was then converted into the carboxylic acid 135 in six steps. Completion of the subunit 131 required conversion into the acid chloride and reaction with the lithium anion of methyl-(di-l,l,l-trifluoroethyl)-phosphonate. The C9-C24 aldehyde 132 was prepared in two steps from 136, an intermediate from previous routes [55-58], The Still-Gennari-type coupling of 131 and 132 was readily achieved via treatment with... 

The Ando variant is an alternative to the Still-Gennari variant of the Horner-Wadsworth-Emmons reaction. Here, phosphonates are employed that contain two aryloxy residues, for example, the ortho-tolyloxy residues of the phosphonate A. The Ar-O groups in this reaction... 

Fig. 11.14. Preparation of tmns- or f-configured a,/3-unsaturated esters by the Horner-Wadsworth-Em mons reaction (left) or preparation of their cis- or Z-isomers by the Still-Gennari variant of it (right). 18-Crown-6 is a so-called crown ether containing a saturated 18-membered ring that is made up from six successive —CH2—0—CH2-units. 18-Crown-6 dissociates the K ions of the Horner-Wadsworth-Emmons reagent by way of complexation.

Fig. 11.15. Analysis of the overall stereoselectivity of a Still—Gennari olefination such as the one in Figure 11.13 simple diastereoselectivity of the formation of the alkoxide intermediate from the achiral phosphonate A and the achiral aldehyde B. For both reagents the terms "back face" and "front face" refer to the selected projection.

Let us now consider the stereostructures C/ent-C of the two enantiomeric Still-Gennari intermediates of Figure 11.15 from another point of view. The simple diastereoselectivity (see Section 11.1.3) with which the phosphonate A and the aldehyde B must combine in order for the alkoxides C and ent-C to be produced is easy to figure out. If we use the formulas as written in the figure, this simple diastereoselectivity can be described as follows the phosphonate ion A and the aldehyde B react with each other in such a way that a back facephosphonate/back faceaidehyde linkaSe (formation of alkoxide C) and a front facephosphonate/front facealdehyde linkage (formation of alkoxide ent-C) take place concurrently. 

We now analyze the Still-Gennari reaction of Figure 11.17. The reagents there are the enantiomerically pure chiral phosphonate A, with which you are familiar from Figure 11.16,... 

Fig. 11.16. Analysis of the simple diastereoselectivity of a Still-Gennari olefination that starts from the enantiomeri-cally pure phosphonate A and the achiral aldehyde B.

Fig. 11.19. Still-Gennari olefination of a racemic a-chi-ral aldehyde with an enan-tiomerically pure phosphonate as kinetic resolution I—Loss of the unreactive enantiomer ent-B of the aldehyde (R stands for the phenylmenthyl group in the Horner-Wadsworth-Emmons products the naming of the products in this figure is in agreement with the nomenclature of Figures 11.17 and 11.18).

A completely analogous kinetic resolution succeeds with the Still-Gennari olefination of Figure 11.20. Here the racemic substrate is a different oc-chiral aldehyde. It carries a sulfon-... 

The Still-Gennari olefination in Figure 11.21 is recommended to anyone who wants to enjoy a third stereochemical dehcacy. The substrate is a dialdehyde that contains oxygenated stereocenters in both a-positions. Nevertheless, this aldehyde is achiral because it has a mirror plane and thus represents a mew-compound. Meso-compounds can sometimes be con-... 

Fig. 11.21. Still-Gennari ole-fi nation of a meso-aldehyde with an enantionmerically pure phosphonate—Conversion of a meso- into an enantiomerically pure compound.

The stereostructure of the alkoxide intermediate of a Horner-Wadsworth-Emmons reaction which finally leads to the trans-o cim was recorded in Figure 9.14 (as formula A). The Still-Gennari variant of this reaction (Figure 9.15) must proceed via an alkoxide with the inverse stereostructure because an olefin with the opposite configuration is produced. According to Figure 9.16, this alkoxide is a 50 50 mixture of the enantiomers C and ent-C. Each of these enantiomers contributes equally to the formation of the finally obtained cw-configured acrylic ester D. 

The Still-Gennari olefinations of Figures 9.17-9.22 start from similar substrates as those shown in Figure 9.16. However, at least one of them is chiral. Since each of these... 

We now analyze the Still-Gennari olefination of Figure 9.18. The reagents there are the enantiomerically pure chiral phosphonate A, with which you are familiar from Figure 9.17, and an enantiomerically pure a-chiral aldehyde B. The diastereoselectivity of the formation of the crucial alkoxide intermediate(s) is in this case determined by the interplay of three factors ... 

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